CN106794215A - For reducing body weight and reducing composition and its pharmaceuticals and the application of body fat - Google Patents
For reducing body weight and reducing composition and its pharmaceuticals and the application of body fat Download PDFInfo
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- CN106794215A CN106794215A CN201580045334.3A CN201580045334A CN106794215A CN 106794215 A CN106794215 A CN 106794215A CN 201580045334 A CN201580045334 A CN 201580045334A CN 106794215 A CN106794215 A CN 106794215A
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Abstract
The present invention discloses a kind of composition and its pharmaceuticals and application for reducing body weight and reduce body fat, said composition includes Green tea extract and turmeric extract, and based on the gross weight of said composition, Green tea extract is respectively 30% to 75% and 20% to 55% with the percentage by weight of turmeric extract.The animal experiment of the first inducing obesity pattern of composition of the present invention or simultaneously in the animal experiment of inducing obesity, compared to single plant extract or commercially available slimming medicine Orlistat is bestowed, all with the effect for substantially reducing body weight and body fat.
Description
The present invention is on a kind of composition, the plant extract of Green tea extract and turmeric extract espespecially comprising specified weight ratio；The present invention is on a kind of application of the composition, the espespecially application by the composition in the pharmaceuticals for reducing body weight and body fat are prepared；The present invention is on a kind of pharmaceuticals for including the composition, espespecially available for the pharmaceuticals for reducing body weight and reduction body fat；The present invention is more on a kind of application of the pharmaceuticals, espespecially by the medicine usable described in effective dose in the application for reducing body weight and body fat.
According to the World Health Organization to fat definition, with body-mass index (Body mass index, BMI overweight (overweight)) is defined as more than 25, BMI is defined as fat (obesity) more than 30, statistics points out that global overweight in 2014 alreadys exceed 2,700,000,000 people with fat population, wherein about 13% population is population of being obese, and the probability of the relevant disease such as these fat people's developing cardiovascular diseases, hyperlipemia, diabetes, cancers also significantly increases than common people.The research report of the World Health Organization is also indicated that, the whole world causes in the disease of mortality risk, overweight and fat ranking the 6th, shown according to data, at least overweight or fat caused chronic disease is died from more than 3,400,000 adults within 2013, wherein having 44% diabetes and 23% ischemic heart disease medical burden to be attributable to obesity.Many data display that there is the trend being gradually reduced at the age of overweight people, and according to the data display of the World Health Organization, it is overweight that the whole world in 2011 there are about less than 10,000 years old children more than 4000.U.S.'s the Johns Hopkins Bloomberg School of Public Health (JohnsHopkins Bloomberg School of Public Health) is pointed out in 2007 annual reports, estimate that there is 75% adult's overweight the whole America in 2015, wherein 41% population belongs to fat, and with the rise of developing country, global population of being obese rapid amplifying will be made, as one of main epidemic disease.U.S. CDC Disease Control Department points out U.S. adults population of being obese more than 72,000,000 people, and the Asian-Pacific area just accounts for 40% in global population of being obese, the overweight and fat ratio of Chinese adult is substantially increased 38.5% by 2010 from 25% in 2002, predict 2015, China by have 50% to 57% population overweight.
Obesity is currently the health problem that the whole world is all paid much attention to, and the reason for research is pointed out to cause obesity is extremely complex, has Multiple Factors to involve wherein.Increasing evidence displays that the simple problem that fat not self-contr ol can just improve, but is related to the complicated symptom of internal Appetite regulation and energetic supersession, is a kind of disease of internal metabolic imbalance.The fat rate that not only causes death is improved and huge medical burden, also have impact on the quality of life of the mankind.Although the fat cause of disease is not established completely, think factor-related with mental community with heredity, metabolism, biochemical, culture.Research shows that the mankind have many causes of the death and obesity to have
Close, including malignant tumour, angiocardiopathy, cranial vascular disease, diabetes, chronic lower respiratory illness, chronic liver disease and hepatic sclerosis, hypertension disease, kidney trouble etc., the problem of display problem of obesity has turned into the whole world all pole must be paid attention to.Fat prevalence rate is more and more high in recent years; and would generally engender the metabolic disorder such as hypertension, hyperglycaemia and insulin resistance and dyslipidemia phenomenon with obesity and cause metabolic syndrome; it is easy to develop into the diseases such as diabetes, angiocardiopathy, arteriosclerosis, cranial vascular disease and cancer; apoplexy or miocardial infarction are caused, in addition it is dead.
The mechanism of action of current loss of weight medicine can be divided mainly into two major classes, and respectively appetite-suppressing and blocking enteron aisle partially absorbs two major classes for food fat.Wherein appetite-suppressing is the main mechanism of past and presently commercially available slimming medicine, this class medicine includes the medicines such as Sibutramine (Reductil), Lorcaserin, Qsymia and Contrave, and side effect is more serious and with a certain degree of cardiovascular risk；By taking undercarriage slimming drugs Sibutramine (Reductil) before as an example, its occupation rate of market is once up to 7 one-tenth, it is to increase satiety by nervous centralis effect with promoting the increased double action of body metabolism rate to reach the effect of weight loss in periphery, Sibutramine is the inhibitor of a kind of norepinephrine (noradrenaline) and thrombocytin (serotonin) recycling, satiety can be increased with appetite-suppressing, reach the purpose of loss of weight, the increase of satiety is the suppression that serotonin and noradrenaline is reabsorbed, acted on by α 1- and β1-adrenergicreceptor (α 1-adrenoceptors or β 1-adrenoceptors) and 5-HT2 receptor subtypes (5-HT2receptor subtypes).The central action of this medicine may result in blood pressure rise and palpitating speed, and have been found to Reductil in recent years and can increase risk of cardiovascular diseases, therefore European Union, the U.S., Australia, TaiWan, China etc. to announce the slimming drugs undercarriage of the composition containing Sibutramine in 2010.
And be then Orlistat for the slimming medicine partially absorbed of food fat by blocking enteron aisle, this is also in the unique legal slimming drugs composition being used for a long time of most of country, it is a kind of with selectivity, reversible intestines and stomach lipolysis enzyme inhibitor, act in stomach and small intestine, serine (serine) position that the lipolytic enzyme secreted with stomach and pancreas is activated at it forms covalent bond, by lipolytic enzyme deactivation, so that lipolytic enzyme can not hydrolyze the free fatty and monoglyceride that the fat existed in diet with triglyceride is converted into being available for absorbing, because undigested triglyceride can not absorb, so will be expelled directly out external, by suppressing pancreas and intestinal fat digestive ferment, and enteron aisle is reduced to the absorption for fat of ingesting up to 25 to 30%.Because Orlistat main effect model is to block fat absorption, therefore during taking medicine it is possible that oil just, defecation frequency increase, the side effect in terms of the intestines and stomach of gaseous distention etc., it can also interfere with fat soluble vitamin absorption, foreign countries also cause hepatic injury, the case of the serious side effects such as gall stone.
High demand, the high profit of loss of weight medicine attract each pharmaceutical factory input research and development, but drug safety is a test of loss of weight medicine, serious drug side-effect and risk of cardiovascular diseases, FDA existing several years before 2012 is caused not check and approve any Xenical, therefore multiple commercial vendors share price even drops sharply, and causes market quiet.Start U.S. FDA within 2012 and have approved 4 Xenicals, respectively Belviq, Qsymia, Contrave and Saxenda successively again finally, it is contemplated that loss of weight pharmaceutical market will be activated once again.
Qysmia and Belviq, its main component is respectively Phentermine-Topiramate (Phentermine-topiramate) and lorcaserin (Lorcaserin), mechanism of action is mainly all to increase satiety, appetite-suppressing, to reach the purpose of loss of weight.Qysmia is containing Phentermine (Phentermine) and the old medicine composition of two kinds of Topiramate (Topiramate), wherein phentermine is to belong to central nervous excitation agent, and the mechanism of its main appetite-suppressing is by allowing brain hypothalamus to stimulate acth secretion norepinephrine；Topiramate mechanism of action is to promote neurotransmitter GABA activity, block sodium-ion channel, antagonism glutamine (glutamine) acceptor and suppress carbonic anhydrase (carbonic anhydrase) to reach appetite-suppressing and increase the effect of satiety.
But just there are 24 subjects cardiac valves problem occur after using the slimming drugs Fen-Phen (fenfluramine/dexfenfluramine-phentermine) containing Phentermine when 1997, also fenfluramine and dexfenfluramine therefore are caused by U.S. FDA requirement undercarriage.Phentermine is because past attempts have and cause serious cardiovascular risk, therefore are still disabled in many countries；Another composition Topiramate is in the past then to be approved the medicine for treating epilepsy.Know that Phentermine-topiramate side effects of pharmaceutical drugs include trick and the situations such as thorn picotement, giddy, dysgeusia, insomnia, constipation and dry occur at present.
Lorcaserin is 5-HT2C receptor activators, by activating hypothalamus melanin cortin neuron (pro-opiomelanocortin neurons, POMC neurons) produce α-MSH (melanocyte stimulating hormone), and then induce generation satiety, appetite-suppressing and the Energy intaking that cuts down one's diet.Lorcaserin is to act on 5-HT2C acceptors by high selectivity, it is low for 5-HT2A and 5-HT2B receptor actings, therefore think that previous serious cardiovascular side effect occurrence risk can be reduced from mechanism, but its related side effect includes cardiac valves damage, headache, nausea, fatigue and urethral infection, therefore FDA remains that dealer need to carry out follow-up clinical monitoring, if need to just disable medicine immediately while taking the continuous 3 months body weight of Lorcaserin and not mitigating.
Naltrexone (Contrave) is a kind of dopamine, norepinephrine resorption inhibition, acts on central nervous system, can appetite-suppressing, Contrave side effects are introgression, nausea, constipation, headache, vomiting, dizziness etc..Saxenda is then the slimming medicine of subcutaneous administrations, Saxenda mechanism of action is mainly the speed by reducing gastric emptying, increase satiety, to reach the purpose of loss of weight, side effect is nausea, hypoglycemia, diarrhoea, constipation, vomiting, headache, loss of appetite etc..Generally speaking, the risk and the security of long-term use that the loss of weight new drug listed at present is produced for angiocardiopathy must still be monitored for more time, therefore the patient for being not suitable for having angiocardiopathy originally takes, and still there is many side effects and security doubt, composition Phentermine contained by especially Qsymia is because past attempts cause serious angiocardiopathy, therefore are still disabled in TaiWan, China and many countries.
The subject matter of slimming drugs application development is the safety issue such as the cardiovascular risk being used for a long time or spirit aspect security doubt, and the side effect such as dizziness, insomnia, palpitaition, constipation and cardiovascular risk also allow many users not pacify for a long time
The heart uses existing slimming medicine.The slimming medicine passed through is checked and approved at present, because side effect is high, the reason such as poor resistance, cardiovascular risk so that loss of weight medicine overall market is not consistent with fat overweight population and the loss of weight demand in the whole world.In from nineteen fifty-seven to 10 slimming medicines of listing in 2014, just have 5 because cause cardiovascular risk or spirit aspect security doubt and undercarriage, its main mechanism is lost weight by appetite-suppressing, and 7 one-tenth Sibutramine (trade name Reductil) to list the rate of accounting for are obtained after being listed comprising 2002.
As can be seen here, the cardiovascular risk that the degree that current slimming medicine still suffers from differs and security doubt, in the market stills need that a kind of security is higher, side effect is low, absent cardiovascular risk doubt and while can effectively lose weight and body fat, and reduces the fat-reducing medicine of cardiovascular danger.
The content of the invention
The present invention provides a kind of plant extracts composition for being used to reduce body weight and body fat, it includes Green tea extract and turmeric extract, and based on the gross weight of plant extracts composition, the percentage by weight of Green tea extract and turmeric extract is respectively 30% to 75% and 20% to 55%.
In preferred embodiment, plant extracts composition of the present invention further includes resveratrol, and the resveratrol accounts for the gross weight of composition for more than 0% to 30%.
Plant extracts composition of the present invention is effectively reduced body weight and body fat.Wherein it is worth noting that, zoopery show individually bestow respectively resveratrol for reduce body weight and body fat it is not effective, individually bestow turmeric extract effect also unobvious, this is consistent with past result of study, and the present invention not only gives plant extracts composition of the present invention simultaneously in inducing obesity process, can be observed plant extracts composition of the present invention have substantially reduce body weight and the effect of body fat, further find, plant extracts composition of the present invention is given again under the obesity mice pattern of inducing obesity, also it can substantially observe that the present invention significantly reduces the effect of mouse weight and body fat, and plant extracts composition of the present invention is compared with commercially available slimming medicine Xenical (Orlistat), the present invention reduces body weight and the effect of body fat, all it is significantly better than commercially available slimming medicine Orlistat (p ＜ 0.001), and the pattern of such a first inducing obesity compared with it is traditional common while inducing obesity zootype, it is more difficult to reduce its body weight and body fat, but also it is overweight with fat situation closer to actual therapeutic human body, plant extracts composition of the present invention, which can still reach, on this condition so substantially reduces body weight and the effect of body fat, and effect significantly surmounts commercially available slimming medicine and single plant extract, reflect that the composition of the present invention not may achieve easily.
According to the present invention, " turmeric extract ", in the extract for referred to including curcumin, the concentration that wherein curcumin (curcumin) accounts for turmeric extract is 80% to 100%；" Green tea extract ", in the extract for referred to including catechin (catechins), the concentration that wherein catechin accounts for Green tea extract is 75% to 100%.
The present invention more provides a kind of method that manufacture includes Green tea extract and the plant extracts composition of turmeric extract, including the plant extracts composition for including Green tea extract and turmeric extract is mixed into capsule, lozenge with pharmaceutically acceptable salt based composition, pharmaceutically acceptable stabilization agent or pharmaceutically acceptable excipient or coating ingot or injection transfusion is made.
Preferably, described method further comprises adding resveratrol, to form the plant extracts composition for including Green tea extract, turmeric extract and resveratrol.
Preferably, described stabilization agent includes but is not limited to xylitol, D-sorbite, polydextrose, hydroxyl isomaltulose and D-glucose.
The present invention further provides the application of the plant extracts composition in the pharmaceuticals for reducing body weight and body fat are prepared for reducing body weight and body fat.
The present invention more provide it is a kind of be used to reduce the pharmaceuticals of body weight and body fat, its described comprising effective dose is used to reducing the plant extracts composition and pharmaceutically acceptable excipient of body weight and body fat.
In preferred embodiment, further included in the pharmaceuticals and effectively reduce body weight and the resveratrol of body fat dosage.
According to the present invention, described " pharmaceutically acceptable excipient " includes but is not limited to disintegrant (disintegrant), binder (binder), filler (filler), lubricant (lubricant), suspending agent (suspending agent), cosolvent (solubilizer) and glidant (glidant).The usage amount of excipient depends on that how many active component and formulation used, and a kind of excipient can perform more than one function.
Preferably, described disintegrant includes but is not limited to agar (agar), alginic acid (alginic acid), calcium carbonate (calcium carbonate), carboxymethyl cellulose (carboxymethylcellulose), cellulose (cellulose), clay (clays), cataloid (colloidal silica), cross-linked carboxymethyl sodium (croscarmellose sodium), PVPP (cross-linked povidone), glue (gum), aluminium-magnesium silicate (magnesium aluminum silicate), methylcellulose (methyl cellulose), polacrilin potassium (polacrilin potassium), mosanom (sodium alginate), low substituted hydroxypropyl cellulose (low substituted hydroxypropyl cellulose), PVPP hydroxypropyl cellulose (crosslinked polyvinylpyrrolidone hydroxypropylcellulose), propyl cellulose (sodium starch glycolate) and starch (starch).
Preferably, described binder includes but is not limited to microcrystalline cellulose (microcrystalline cellulose), hydroxymethyl cellulose (hydroxymethyl cellulose), hydroxypropyl cellulose (hydroxypropyl cellulose) and polyvinylpyrrolidone (polyvinyl pyrrolidone).
Preferably, described filler include but is not limited to calcium carbonate (calcium carbonate), calcium phosphate (calcium phosphate), calcium monohydrogen phosphate (dibasic calcium phosphate), tricresyl phosphate calcium sulfate (tribasic calcium sulfate),
Calcium carboxymethylcellulose (calcium carboxymethylcellulose), cellulose (cellulose), dextrin (dextrin), salt (salt), dextrin (dextrin), dextrose (dextrose), fructose (fructose), lactitol (lactitol), lactose (lactose), carbonate (carbonate), magnesia (magnesium oxide), maltitol (maltitol), maltodextrin (maltodextrin), maltose (maltose), D-sorbite (sorbitol), starch, sucrose (sucrose), sugared (sugar) and xylitol (xylitol).
Preferably, described lubricant includes but is not limited to agar, calcium stearate (calcium stearate), ethyl oleate (ethyl oleate), ethyl laurate (ethyl laurate), glycerine (glycerin), glyceryl palmitostearate (glyceryl palmitostearate), hydrogenated vegetable oil (hydrogenated vegetable oil), magnesia (magnesium oxide), magnesium stearate (magnesium stearate), mannitol (mannitol), poloxamer (poloxamer), ethylene glycol (ethylene glycol), sodium benzoate (sodium benzoate), NaLS (sodium lauryl sulfate), odium stearate (sodium stearoyl acid), D-sorbite, stearic acid (stearic acid), talcum (talc) and zinc stearate (zinc stearate).
Preferably, described suspending agent is including but not limited to mannitol, carboxymethyl cellulose (carboxymethyl cellulose, CMC) and sodium carboxymethylcellulose (CMC-Na).
Preferably, described cosolvent is including but not limited to hydroxypropyl beta cyclodextrin (hydroxypropyl-beta-cyclodextrin), Tween 80 (tween 80), castor oil (castor oil) and polyethylene glycol (PEG).
Preferably, described glidant includes but is not limited to the materials such as magnesium stearate (magnesium stearate), silica (silicon dioxide), magnesium trisilicate (magnesium trisilicate), powdered cellulose (powdered cellulose), starch, talcum, tricalcium phosphate (tribasic calcium phosphate), calcium silicates (calcium silicate), magnesium silicate (magnesium silicate), cataloid and Silica hydrogel (silicon hydrogel).
Pharmaceuticals of the present invention can exist in a variety of forms.These forms include but is not limited to liquid, semi-solid and solid dosage forms, such as liquid solution (such as injectable and infusible solutions), dispersion liquid or suspension, lozenge, pill, pulvis, liposome and suppository.Preferably form depends on expected mode of administration and treatment use；Preferably, the pharmaceuticals of the present invention are to be in orally available or infusible solutions form.In an embodiment of the present invention, the composition of Green tea extract of the pharmaceuticals comprising effective dose and turmeric extract for reducing body weight and body fat is to be applicable by oral administration, and according to the plant extracts composition of the present invention and had tablet, particle, coating ingot, capsule, lozenge and other solid oral dosage forms to be also covered by the scope of the invention by the peroral dosage form of preference.
The present invention more provide it is a kind of with the medicine usable in the application for reducing body weight and body fat, it is to bestow acceptor by the pharmaceuticals for including Green tea extract and the plant extracts composition of turmeric extract of effective dose, and acceptor is the mankind or animal.To reach the effect for reducing body weight and body fat.
Preferably, it is oral administration or injection administration to bestow mode.
Preferably, effective dose refers to that daily per kilogram bestows acceptor 1.8mg to 145mg pharmaceuticals, acceptor is herein
The mankind or animal, the preferably mankind.
Preferably, effective dose refers to that daily per kilogram bestows acceptor 5.4mg to 70mg pharmaceuticals, acceptor is the mankind or animal, the preferably mankind herein.
According to the present invention, " effective dose " extrapolates the effective dose of not isoacceptor in the table 1 (Table 1) of " the estimating the maximum Safety Starting Dose (estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers) of adult in initial clinical experience " that can be announced according to Food and Drug Administration (food and drug administration, FDA) herein.
According to the present invention, " reducing body weight and body fat " is such as referred to herein as through after the composition for including Green tea extract and turmeric extract for bestowing effective dose, or further after the composition comprising resveratrol, body weight and body fat are all respectively less than fat control group, it is such as the example of the present invention, reducing body fat can be by bestowing the Green tea extract of particular range amount and the composition of turmeric extract, or further include the composition of resveratrol, and in the peripheral fat mass of measurement epididymis in particular time range, kidney periphery fat mass, mesenterium periphery fat mass, fat mass outside groin and cavum peritoneale changes and obtained.
The each component of the plant extracts composition of the present invention is all obtained by plant extraction, experimental result shows that plant extracts composition of the present invention does not interfere with appetite or food ration, also the safety index of other serum biochemistries is not interfered with, therefore security is higher, it is safer also without apparent side effect compared to other loss of weight medicines on the market at present.In addition, compared to prior art slimming medicine appetite-suppressing or by way of blocking intestinal fat to absorb to reduce heat absorption to reach the effect that loses weight, plant extracts composition of the present invention can not only lose weight, it more can effectively suppress the hyperplasia of body fat cell, body fat metabolism and energy utilization can also be increased simultaneously, and improved for fat basic reason, to reduce the multiple fat problem that loss of weight is common, and a variety of cardiovascular danger indexs such as Lipid and blood glucose can be improved, reduce cardiovascular risk.
It can thus be appreciated that plant extracts composition of the present invention more can be for the fat higher and can effectively reduce body weight and the scheme of body fat there is provided a security with overweight problem of the whole world at present, future can be applied to the purposes such as related pharmaceutical product or health food.
Fig. 1 detects block diagram of each group for forerunner's adipocytic cell growth inhibition for the present invention with cell viability assays (MTT assay).
Fig. 2 detects block diagram of each group for adipocytic cell growth inhibition in differentiation for the present invention with cell viability assays (MTT assay).
The block diagram that increased weights of Fig. 3 A for the present invention by inducing obesity simultaneously with administration to detect each group mouse changes.
Fig. 3 B for the present invention by inducing obesity simultaneously with administration to detect the interior fat of each group mouse, subcutaneous fat and total
The block diagram of the fat weight change of fat mass.
The block diagram that increased weights of Fig. 4 A for the present invention by being administered again after first inducing obesity to detect each group mouse changes.
The block diagram that Fig. 4 B are changed for the present invention by being administered again after first inducing obesity with the fat weight of the interior fat, subcutaneous fat and total fat mass that detect each group mouse.
The tendency chart that increased weights of Fig. 5 A for the present invention by inducing obesity simultaneously with administration to detect each group rat changes.
Fig. 5 B for the present invention by simultaneously inducing obesity with administration with detect each group rat interior fat change block diagram.
With the following drawings and preferred embodiments of the present invention, the present invention is expanded on further to reach the technological means that predetermined goal of the invention is taken.
The forerunner's adipocytic cell growth Inhibition test of embodiment 1.
The present embodiment is by forerunner's fat cell 3T3-L1 with every hole 1 × 104Cell (cells/well) is incubated at 96 porose discs,-DMSO the solvent control groups in addition to control group, plant extracts composition ME008A, ME008D, ME001, ME00C1 and ME00D1 of 50ppm resveratrols, 50ppm turmerics extract, 80ppm Green tea extracts and the 100ppm present invention, experiment totally 9 groups and every group of repetition of experiment progress 3 are separately added into different holes.After being cultivated 48 hours after dosing, cell growth condition is photographed to record, and each substances are analyzed for 3T3-L1 forerunner's adipocytic cell growth inhibition with cell viability assays (MTT assay).Wherein control group is solvent control group DMSO, the plant extracts composition ME008A of the present invention includes 50wt% Green tea extracts, the green coffee bean extracts of 25wt% and 25wt% resveratrols, ME008D includes 40wt% Green tea extracts, the green coffee bean extracts of 45wt% and 15wt% resveratrols, ME001 includes 60wt% Green tea extracts, 10wt% turmerics extract and 30wt% resveratrols, ME00C1 includes 40wt% Green tea extracts, 50wt% turmerics extract and 10wt% resveratrols, and ME00D1 includes 75wt% Green tea extracts and 25wt% turmeric extracts.Each group of data is represented with average value ± SD (Mean ± SD), English alphabet a, b, c, d, e, f, g represent the result of statistics, have statistically difference (p ＜ 0.05) between different letter expression groups, same letter does not then have statistical discrepancy (p ＞ 0.05) between expression group.
As a result it is as shown in Figure 1, compared with control group, tri- groups of plant extracts composition ME00C1, ME001 and ME008D of the present invention can all significantly inhibit forerunner's adipocytic cell growth (p ＜ 0.05), it is again optimal (p ＜ 0.05) for the growth inhibitory effect of forerunner's fat cell with ME00C1 among plant extracts composition each group wherein of the present invention, and composition ME00C1 for forerunner's fat cell growth inhibitory effect also substantially than individually bestowing resveratrol, turmeric extract or Green tea extract more preferably (p ＜ 0.05).
Adipocytic cell growth Inhibition test during embodiment 2. is broken up
The present embodiment is by 3T3-L1 with 1 × 105Cells/well is incubated at 12 porose discs, culture was used instead to the 4th day containing every milliliter of 5 micrograms (μ g/ml) differentiation agent insulin, 1 micromole's volumetric concentration (μM) dexamethasone (dexmethasone), the nutrient solution of the 3-isobutyl-1-methylxanthine (3-isobutyl-1-methylxanthine) of 0.5 mM of volumetric concentration (mM) is broken up with inducing adipocyte,-DMSO the solvent control groups in addition to control group, each group is separately added into 50ppm resveratrols, 50ppm turmeric extracts, 80ppm Green tea extracts and 100ppm plant extracts composition ME008A of the present invention, ME008D, ME001, ME00C1, ME00D1 is to be tested, experiment totally 9 groups and every group of repetition of experiment progress 3.After being cultivated 48 hours after dosing, cell growth condition is photographed to record, and inhibition of each Test Materials for fat cell in differentiation is analyzed with cell viability assays (MTT assay).Each group of data is represented with average value ± SD (Mean ± SD), English alphabet a, b, c, d, e, f represent the result of statistics, have statistically difference (p ＜ 0.05) between different letter expression groups, same letter does not then have statistical discrepancy (p ＞ 0.05) between expression group.
As a result it is as shown in Figure 2, compared with control group, each plant extracts composition of the present invention can all significantly inhibit adipocytic cell growth (p ＜ 0.05) in differentiation, it is again optimal (p ＜ 0.05) for the inhibition of adipocytic cell growth in differentiation with ME00C1 among plant extracts composition each group wherein of the present invention, and composition MEOOC1 for fat cell in differentiation growth inhibitory effect also substantially than individually bestowing resveratrol, turmeric extract or Green tea extract more preferably (p ＜ 0.05).
The zoopery I of embodiment 3. (while inducing obesity and administration)
This experimental example uses 8 week old B6 strain female mices, and it is divided into Normal group, fat control group, resveratrol group (61.5mg/kg B.W.), Green tea extract group (123mg/kg B.W.), totally 5 groups of the plant extracts composition ME001 (676.5mg/kg B.W.) of the present invention, every group is respectively tested using 5 jennies, during experiment, in addition to Normal group feeding chow diet, all continuous 8 weeks of remaining each group is with high lipid food feeding, to induce obesity symptom, and daily pipe is fed for and gives substances 8 weeks simultaneously, fat control group, which is then managed, feeds isometric sterilized water, to assess the difference of each group mouse weight and body fat.The body weight and average food ration of every animal are recorded in experimentation weekly, after the completion of experiment, mouse is sacrificed, take the peripheral fat of its ovary, kidney periphery fat, the peripheral fat of mesenterium to weigh and calculate its visceral fat mass, take the fat outside its groin and cavum peritoneale to be weighed to calculate subcutaneous fat amount.Each group of data is represented with average value ± SD (Mean ± SD), English alphabet a, b, c, d, e, f represent the result of statistics, have statistically difference (p ＜ 0.05) between different letter expression groups, same letter does not then have statistical discrepancy (p ＞ 0.05) between expression group.
Result of the test is as shown in Fig. 3 A, Fig. 3 B, compared with fat control group, plant extracts composition ME001 body weight total augment weight of the present invention then substantially reduces (p ＜ 0.05), reduction amplitude is 47.2%, therefore, plant extracts composition ME001 of the present invention can effectively reach the effect (p ＜ 0.05) lost weight.It is on the contrary, the mouse of resveratrol group its body weight total augment weight, visceral fat mass, subcutaneous fat amount and body fat gross weight (comprising interior fat and subcutaneous fat) are individually bestowed, compared to fat control group then all without statistical discrepancy (p ＞ 0.05).
No matter plant extracts composition ME001 of the present invention is then all remarkably decreased (p ＜ 0.05) compared with fat control group in visceral fat weight, subcutaneous fat weight or body fat gross weight.In addition, plant extracts composition ME001 of the present invention is compared with other each groups, ME001 not only can be effectively lost weight with reducing body fat, and effect is all better than single plant extract group (p ＜ 0.05), with preferably loss of weight effect.
The each group mouse of feeding high lipid food during experiment, its food ration that is averaged weekly has no statistical discrepancy (p ＞ 0.05).
The zoopery II of embodiment 4. (first inducing obesity is administered again)
The present embodiment uses 8 week old B6 strain female mices, in addition to Normal group feeding chow diet, other mouse first continuous 6 weeks are with high lipid food feeding, inducing turns into after obesity mice (obesity mice body weight increases above 20% compared with original body mass), obesity mice is randomly divided into 7 groups, include fat control group, Xenical medicine control group (34.8mg/kg B.W.), turmeric extract group (41mg/kg B.W.), and 4 groups of the plant extracts composition test group of the present invention, include ME008A (676.5mg/kg B.W.), ME008D (676.5mg/kg B.W.), ME001 (676.5mg/kg B.W.) or ME00C1 (651.9mg/kg B.W.), every group is respectively tested using 5 jennies, in addition to Normal group, remaining 7 groups of obesity mice persistently gives high lipid food and feeds mode daily with pipe again gives substances 8 weeks, fat control group is then given isometric sterile water pipe and fed, sacrificed after amounting to 14 weeks high lipid foods of feeding altogether, to assess the difference of the projects such as each group mouse weight and body fat.The body weight and average food ration of every animal are recorded in experimentation weekly, after the completion of experiment, mouse is sacrificed, take the peripheral fat of its ovary, kidney periphery fat, the peripheral fat of mesenterium to weigh and calculate its visceral fat mass, take the fat outside its groin and cavum peritoneale to be weighed to calculate subcutaneous fat amount.Each group of data is represented with average value ± SD (Mean ± SD), English alphabet a, b, c, d, e represent the result of statistics, have statistically difference (p ＜ 0.05) between different letter expression groups, same letter does not then have statistical discrepancy (p ＞ 0.05) between expression group.
Result of the test is as shown in Fig. 4 A, Fig. 4 B, compared with Normal group, the mouse weight weightening of fat control group all substantially increases (p ＜ 0.05) with body fat, its weight gain increasing degree is up to 87.7%, represents that successful inducing mouse body weight rising causes obesity to the present embodiment.Compared with fat control group, plant extracts composition ME008D, ME001 and ME00C1 of the present invention body weight evolution are all significantly reduced (p ＜ 0.05), wherein again with plant extracts composition ME00C1 best results of the present invention, and effect is significantly better than commercially available slimming drugs Xenical (Orlistat) (p ＜ 0.05) and turmeric extract (p ＜ 0.05).
Compared with fat control group, plant extracts composition ME008D, ME001 and ME00C1 of the present invention body fat (including interior fat and subcutaneous fat) are also significantly reduced (p ＜ 0.05), its body fat reduction amplitude is respectively 10.3%, 36.9% and 64.1%, wherein again with plant extracts composition ME00C1 best results of the present invention, and it is significantly better than commercially available slimming drugs Xenical (p ＜ 0.05) and turmeric extract (p ＜ 0.05).Display plant extracts composition ME00C1 of the present invention has the effect for preferably losing weight and reducing body fat for fat mouse.The each group mouse of feeding high lipid food during experiment, its food ration that is averaged weekly has no statistical discrepancy (p ＞ 0.05).
The zoopery III of embodiment 5. (while inducing obesity and administration)
This experimental example uses 8 week old SD strain male rats, and it is divided into Normal group, fat control group, totally 4 groups of plant extracts composition ME00C1 (199.6mg/kg B.W.) of the present invention and ME00C1A (186mg/kg B.W.), wherein plant extracts composition ME00C1A includes 55.5wt% Green tea extracts and 44.5wt% turmeric extracts, every group is respectively tested using 6 rats, during experiment except normally to group with chow diet feeding in addition to, all continuous 8 weeks of its excess-three group is with high lipid food feeding, to induce obesity, daily pipe, which is fed for, simultaneously gives substances, fat control group is then given isometric sterile water pipe and fed, to assess the difference of the projects such as each group mouse weight and interior fat.The body weight and average food ration of every animal are recorded in experimentation weekly, after the completion of experiment, rat is sacrificed, takes the peripheral fat of its epididymis, kidney periphery fat, the peripheral fat of mesenterium to weigh and calculate its visceral fat mass.Each group of data is represented with average value ± SD (Mean ± SD), English alphabet a, b, c, d represent the result of statistics, have statistically difference (p ＜ 0.05) between different letter expression groups, same letter does not then have statistical discrepancy (p ＞ 0.05) between expression group.
Result of the test is as shown in Figure 5A, compared with fat control group, the rat body weight total augment weight for bestowing plant extracts composition ME00C1 and ME00C1A of the present invention is all decreased obviously, compared with fat control group, plant extracts composition ME00C1 weight gains of the present invention substantially reduce 23.0% (p ＜ 0.01t-test), and plant extracts composition ME00C1A weight gains can more substantially reduce 29.8% (p ＜ 0.001t-test).Experimental result shown in Fig. 5 B is also shown, compared with fat control group, the interior fats such as plant extracts composition ME00C1A of the present invention rat epididymis periphery, kidney periphery and mesenterium periphery are all significantly reduced (p ＜ 0.05), the total fat weight of its internal organ can be reduced up to 35.7%, show that plant extracts composition ME00C1A of the present invention loses weight the best results with body fat.
Described above is only presently preferred embodiments of the present invention, any formal limitation not is done to the present invention, although the present invention is disclosed above with preferred embodiment, but it is not limited to the present invention, any those skilled in the art, in the range of technical solution of the present invention is not departed from, when the technology contents using the disclosure above make a little change or are modified to the equivalent embodiment of equivalent variations, in every case it is the content without departing from technical solution of the present invention, any simple modification that technical spirit according to the present invention is made to above example, equivalent variations and modification, in the range of still falling within technical solution of the present invention.
Claims (8)
- A kind of plant extracts composition for being used to reduce body weight and body fat, it is characterized in that, it includes Green tea extract and turmeric extract, and based on the gross weight of plant extracts composition, the percentage by weight of Green tea extract and turmeric extract is respectively 30% to 75% and 20% to 55%.
- Plant extracts composition according to claim 1, it is characterised in that it further includes resveratrol, and the resveratrol accounts for the gross weight of composition for more than 0% to 30%.
- Application of the plant extracts composition in the pharmaceuticals for reducing body weight and body fat are prepared a kind of described in claim 1 or 2.
- A kind of pharmaceuticals for being used to reduce body weight and body fat, it is characterised in that its acceptable excipient comprising the plant extracts composition described in effective dose claim 1 or 2 and pharmaceutically.
- A kind of pharmaceuticals of claim 4 are reducing body weight and the application in body fat, it is characterised in that pharmaceuticals are bestowed into acceptor with effective dose, acceptor is the mankind or animal.
- Application according to claim 5, it is characterised in that bestow mode and bestowed for oral or injection system.
- Application according to claim 6, it is characterised in that pharmaceuticals are bestowed into the effective dose of acceptor between acceptor per kilogram 1.8mg/KG to 145mg/KG with oral way or injection system.
- Application according to claim 7, it is characterised in that pharmaceuticals are bestowed into the effective dose of acceptor between acceptor per kilogram 5.4mg/KG to 70mg/KG with oral way or injection system.
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| PCT/CN2015/088338 WO2016029868A1 (en) | 2014-08-28 | 2015-08-28 | Composition and medicinal product for reducing body weight and body fat, and use of said product |
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| US10226503B2 (en) | 2014-08-28 | 2019-03-12 | Caliway Biopharmaceuticals Co., Ltd. | Plant extract composition for reducing topical fat and promoting weight loss as well as applications thereof |
| JP6473505B2 (en) | 2014-08-28 | 2019-02-20 | カリウェイ バイオファーマシューティカルズ カンパニー リミテッド | Compositions used for local fat and weight loss and their pharmaceuticals and uses |
| US10537548B2 (en) | 2014-08-28 | 2020-01-21 | Caliway Biopharmaceuticals Co., Ltd. | Composition and medical product for reducing body weight and body fat, and use of said product |
| US11318110B2 (en) | 2015-08-28 | 2022-05-03 | Caliway Biopharmaceuticals Co., Ltd. | Pharmaceutical composition for reducing local fat and uses thereof |
| AU2016314546C1 (en) * | 2015-08-28 | 2021-07-22 | Caliway Biopharmaceuticals Co., Ltd. | Pharmaceutical composition used for reducing localised fat and use of pharmaceutical composition |
| EP3603628A4 (en) * | 2017-03-28 | 2020-12-02 | Caliway Biopharmaceuticals Co., Ltd. | Composition for reducing weight and reducing body fat and pharmaceutical product and application thereof |
| US20220143126A1 (en) * | 2019-03-31 | 2022-05-12 | Shankaranarayanan JEYAKODI | Synergistic combination of phytoactives |
| KR102137136B1 (en) * | 2019-11-29 | 2020-08-13 | 주식회사 어바웃굿즈 | Composition comprising pumpkin hydrolysis extract, amorphophallus paeoniifolius hydrolysis extract, curcuma extract and cacao nibs extract |
| KR20220147743A (en) | 2021-04-27 | 2022-11-04 | 강원대학교산학협력단 | Composition for treatment or prevention of metabolic diseases containing mixture of gamma poly-γ-glutamic acid(γ-PGA) and levan as active ingredients |
| KR20230114107A (en) * | 2022-01-24 | 2023-08-01 | 연세대학교 산학협력단 | Composition for prevention or treatment of cardiovascular disease |
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| KR20170044196A (en) | 2017-04-24 |
| AU2018278907B2 (en) | 2020-08-13 |
| MX2017002584A (en) | 2017-05-25 |
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| US10537605B2 (en) | 2020-01-21 |
| EP3187189B1 (en) | 2020-11-18 |
| JP2017525771A (en) | 2017-09-07 |
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| CA2960075C (en) | 2021-02-09 |
| AU2015309351A1 (en) | 2017-03-30 |
| KR101923840B1 (en) | 2019-02-27 |
| EP3187189A4 (en) | 2018-04-11 |
| AU2015309351B2 (en) | 2019-01-03 |
| JP6446552B2 (en) | 2018-12-26 |
| WO2016029868A1 (en) | 2016-03-03 |
| ES2851680T3 (en) | 2021-09-08 |
| US20170157194A1 (en) | 2017-06-08 |
| TW201707722A (en) | 2017-03-01 |
| CA2960075A1 (en) | 2016-03-03 |
| AU2018278907A1 (en) | 2019-01-03 |
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